Fig. 7
ABv treatment with anti-PD-1 immunotherapy offers durable therapeutic response. a Treatment protocol for syngrafted WapMyc tumors. The mice received vehicle, venetoclax, metformin, or venetoclax+metformin (ABv) for 21 days. Tumors were surgically removed, and mice were given adjuvant treatments. ABv was given every day for 1 week, and control IgG or anti-PD-1 was given every third day, four times in total. The mice were followed up until the tumors reached Ø 2 cm. Flow cytometry-based immunoprofilings were done after the adjuvant treatment and after the follow-up. b Tumor growth during the neoadjuvant treatment. Student’s t-test (unpaired), SEM. N = 8 mice/treatment group. c Tumor volume during the adjuvant treatment (d7 from surgery). Student’s t-test (unpaired), SD. N = 4 mice/treatment group. d Tumor volume after the adjuvant treatment (d14 from surgery). Student’s t-test (unpaired), SD. e Box plot of tumor volumes in ABv+IgG- vs anti-PD-1-treated groups during and after the adjuvant treatment. After the adjuvant treatment, the only tumor in the ABv+anti-PD-1 group was surgically biopsied for immunoprofiling. f Tumor immunoprofiles after the adjuvant treatment. The heatmap shows fold-changes compared to vehicle+IgG. N = 4 mice/group, except N = 1 in the biopsy. Cell populations derived from parental populations with less than 90 cells are marked with asterisk (*). g Survival of the mice. P-value: Difference between vehicle+IgG and ABv+anti-PD-1-treated mice. h Total white blood cell (WBC) and red blood cell (RBC) counts in the treatment groups. Student’s t-test (unpaired), SD. i Liver injury measured by plasma ALAT levels. Student’s t-test (unpaired), SD. j Average tumor sizes during (d11) adjuvant treatment with vehicle+anti-PD-1, paclitaxel+anti-PD-1, or ABv+anti-PD-1, and after the drug withdrawal (d15). Length of one treatment cycle is 10 days. p-value denotes the difference between post-adjuvant vehicle+anti-PD-1 and ABv+anti-PD-1. N = 3 (vehicle+anti-PD-1), 7 (Paclitaxel+anti-PD-1), 10 (1 cycle of ABv+anti-PD-1). SD, student’s t-test. k Survival of the mice. N = 6 (Paclitaxel+anti-PD-1), 2 (1 cycle of ABv+anti-PD-1), 3 (3 cycles of ABv+anti-PD-1)
